title: Short transmembrane domains with high-volume exoplasmic halves determine retention of Type II membrane proteins in the Golgi complex.
abstract: It is still unclear why some proteins that travel along the secretory pathway are retained in the Golgi complex whereas others make their way to the plasma membrane. Recent bioinformatic analyses on a large number of single-spanning membrane proteins support the hypothesis that specific features of the transmembrane domain (TMD) are relevant to the sorting of these proteins to particular organelles. Here we experimentally test this hypothesis for Golgi and plasma membrane proteins. Using the Golgi SNARE protein Sft1 and the plasma membrane SNARE protein Sso1 from Saccharomyces cerevisiae as model proteins, we modified the length of their TMDs and the volume of their exoplasmic hemi-TMD, and determined their subcellular localization both in yeast and mammalian cells. We found that short TMDs with high-volume exoplasmic hemi-TMDs confer Golgi membrane residence, whereas TMDs with low-volume exoplasmic hemi-TMDs, either short or long, confer plasma membrane residence to these proteins. Results indicate that the shape of the exoplasmic hemi-TMD, in addition to the length of the entire TMD, determine retention in the Golgi or exit to the plasma membrane of Type II membrane proteins.
authors.affiliation: Centro de Investigaciones en Química Biológica de Córdoba, CIQUIBIC (CONICET) and Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Quiroga
authors.forename: Alejandra
authors.initials: A
authors.lastname: Trenchi
authors.forename: Ayelén
authors.initials: A
authors.lastname: González Montoro
authors.forename: Javier
authors.initials: J
authors.lastname: Valdez Taubas
authors.forename: Hugo J F
authors.initials: HJ
authors.lastname: Maccioni
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D003412:Cricetulus; D015966:Gene Expression Regulation, Fungal; D006056:Golgi Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D050765:Qa-SNARE Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D050767:Qc-SNARE Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D050765:Qa-SNARE Proteins; D050767:Qc-SNARE Proteins; D011993:Recombinant Fusion Proteins; C094380:SFT1 protein, S cerevisiae; C084006:SSO1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins
keywords: Golgi; SNAREs; Traffic; Transmembrane domain; Yeast